Acute myocardial infarction is a major cause of mortality and disability worldwide. In patients with myocardial infarction, the treatment option for reducing acute myocardial ischemic injury and limiting myocardial infarction size is timely and effective myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (pPCI).
Although reperfusion therapy during acute myocardial infarction with percutaneous coronary intervention (PCI) or thrombolysis salvages myocardium that would ultimately die without reperfusion, rapidly restoring blood flow to myocardium can also cause lethal injury to vulnerable myocardial cells (i.e., reperfusion injury). The restoration of blood flow can lethally compromise oxygen-deprived cells. Reperfusion injury may offset the optimal salvage of myocardium achieved by PCI and/or thrombolysis. Over the last 20 years extensive research efforts have been devoted to develop therapeutic strategies to prevent reperfusion injury.
There is still a need for additional methods for the treatment of cardiac and cardiovascular disorders and myocardial reperfusion injury by limiting infarct-size through post-ischemia reperfusion injury.
Due to its antioxidant and free-radical scavenger properties, the use of melatonin in the treatment of myocardial infarction has been hypothesized (e.g. A. Dominguez-Rodriguez et al. Contemporary Clinical Trials 2007, 532-539). However, in a clinical proof-of-concept trial, A. Dominguez-Rodriguez et al. (J. Pineal Res. 2017, 62: e12374) found that melatonin failed to reduce myocardial infarct size (MIS) compared with placebo and had an unfavorable effect on the ventricular volumes and LVEF evolution among patients with ST-segment elevation myocardial infarction (STEMI).
Similarly, Ekeløf et al. (Heart Vessels 2016, 31(1), 88-95) found that combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury in a closed-chest porcine model.
Infarct size is a major predictor of post-STEMI mortality and morbidity, and there is still a need for adjunct therapies to PCI that reduce the extent of myocardial damage associated with reperfusion.